1. Field of the Invention
This invention relates to pharmacologically active agents which are encapsulated within protective proteinoid microspheres and the administration of same to warm blooded animals. It relates particularly to orally administered microspheres containing pharmacological agents which otherwise would be deactivated in the gastrointestinal tract.
2. Description of the Prior Art
The available modes of delivery of pharmceutical and therapeutic agents often are severely limited by chemical or physical barriers or both, which are imposed by the body. For example, oral delivery of many such agents would be the general method of choice if not for the numerous barriers faced by these agents along this route. Gastrointestinal conditions of inappropriate pH, the presence of powerful digestive enzymes, the permeability properties of gastrointestinal membranes and tissues and other factors all play important roles in determining the feasibility of oral delivery of active agents to their targets. Among the numerous pharmacological agents which are known to be adversely affected or rendered ineffective when administered orally are the biologically active polypeptides and proteins, such as insulin. These agents are rapidly destroyed in the stomach by acid hydrolysis and in the stomach and lower gastrointestinal tract by enzymes capable of cleaving peptide bonds and, in addition, they pass poorly, if at all, through the gastrointestinal wall.
A great deal of effort has been concentrated on the modification or isolation of the deleterious conditions within the gastrointestinal tract so that a pharmacological agent, which otherwise would be labile, could be absorbed through the stomach or intestine wall intact and in pharmacologically active form. The search in this area has been directed primarily in three directions; the co-administration of adjuvants, such as the resorcinols and the non-ionic surfactants polyoxyethylene oleyl ether and n-hexadecyl polyethylene ether; the co-administration of enzymatic inhibitors, such as pancreatic trypsin inhibitor, diisopropylfluorophosphate (DFP) and trasylol; and the use of liposomes, such as water-in-oil-in-water emulsions which provide a protective layer of lipid around the encorporated pharmacological agent and which represent the most successful approach to date. For example, the use of liposomes containing heparin is disclosed in U.S. Pat. No. 4,239,754 and several studies have been directed to the use of liposomes containing insulin; e.g., Patel et al, FEBS Letters, 62, 60 (1976) and Hashimoto et al, Endocrinol. Japan, 26, 337 (1979). In spite of these demonstrations of limited operability, the use of liposomes is still in the development stage and there are continuing problems, including poor stability and inadequate shelf life.
Accordingly, there remains a need for improved means for targeting the release of active pharmacological agents in the body and particularly for more satisfactory means for oral administration of pharmacological agents which are labile to conditions in the gastrointestinal tract.